Bone marrow derived mesenchymal stem cells (MSCs) have been shown capable of differentiating down several tissue lineages, including bone, cartilage, fat, and tendon. For this reason these cells have been demonstrated as effective contributors in tissue-engineered applications for regenerative therapeutics, particularly in the areas of musculoskeletal repair. Using marrow aspirate MSCs can be easily isolated from a patient, expanded ex vivo, and reintroduced for therapeutic purposes. The use of MSCs in such tissue-engineering strategies relies heavily on both successful MSC proliferation as well as maintaining the ability for these proliferative cells to differentiate down mesenchymal lineages. Moreover, inducing controllable MSC proliferation in vivo proves advantageous in mimicking native healing cascades while ensuring the presence of an ample cell population to effectively contribute to injury remodeling. Such strategies enable tissue-engineering therapeutics to be achieved in regenerative medicine applications.
Currently MSCs can be expanded in vitro, using serum supplements (fetal bovine serum, autologous serum, platelet lysate, feeder-cells) but these approaches are transient in nature, require continual application in vitro, and often yield a highly heterogeneous MSC population. Furthermore, during extended culture, required to attain a therapeutically relevant cell number due to limited MSC numbers in bone marrow, cells exhibit an increasingly senescent phenotype, reduced proliferation, impaired homing capacity, and diminished differentiation potential. Reduced proliferative capacity in particular equates to a diminished long-term regenerative potential once these cells are transplanted for therapeutic purposes.